Browsing by Author "Chanda, Adrita"

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial diseases. The manifestations are tissue-specific and correlate with the mutation load of mitochondrial DNA (mtDNA), known as heteroplasmy. While cerebrovascular events constitute one of the manifestations of the disease, the role of endothelial cells (ECs) in disease pathogenesis is not yet fully understood. In this study, we utilized human induced pluripotent stem cell (hiPSC) derived ECs carrying the 3243A>G mutation as a model for investigating endothelial dysfunction in MELAS. Here, we report a distinct cell morphology among hiPS-ECs carrying a high mutational load in comparison to isogenic controls. In addition, gene expression analysis revealed a heteroplasmy-associated upregulation of genes related to angiogenesis and the insulin-like growth factor (IGF) pathway in MELAS hiPS-ECs. Our data suggests that heteroplasmy-trigged transcriptomic and phenotypic changes in ECs might serve as a mechanism behind the endothelial dysfunction seen in MELAS patients.